ArticleGene therapy2002
A novel conditional Akt 'survival switch' reversibly protects cells from apoptosis.
Article in Gene therapy, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 48 citations in OpenAlex.
- Synthetic Biology: Emerging Concepts to Design and Advance Adeno-Associated Viral Vectors for Gene Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Synthesis and biological evaluation of rapamycin-derived, next generation small molecules.MedChemComm · 2018Review
- Innate and Adaptive Immune Response in Fabry Disease.JIMD reports · 2015Article
- The dual PI3K/mTOR inhibitor PKI-587 enhances sensitivity to cetuximab in EGFR-resistant human head and neck cancer models.British journal of cancer · 2014Article
- Nrf2 deficiency promotes apoptosis and impairs PAX7/MyoD expression in aging skeletal muscle cells.Free radical biology & medicine · 2014Article
- PI-3 kinase p110β: a therapeutic target in advanced prostate cancers.American journal of clinical and experimental urology · 2014Review
- Binding of a sialic acid-recognizing lectin Siglec-9 modulates adhesion dynamics of cancer cells via calpain-mediated protein degradation.The Journal of biological chemistry · 2013Article
- Manipulating signaling at will: chemically-inducible dimerization (CID) techniques resolve problems in cell biology.Pflugers Archiv : European journal of physiology · 2013Review
- Acute depletion of plasma membrane phospholipids-dissecting the roles of PtdIns(4)P and PtdIns(4,5)P2.Journal of chemical biology · 2012Article
- The Akt1 isoform is required for optimal IFN-β transcription through direct phosphorylation of β-catenin.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- DEPTOR ubiquitination and destruction by SCF(β-TrCP).American journal of physiology. Endocrinology and metabolism · 2012Review
- mTOR inhibitors and its role in the treatment of head and neck squamous cell carcinoma.Current treatment options in oncology · 2012Review
- Activation of Wnt signaling by chemically induced dimerization of LRP5 disrupts cellular homeostasis.PloS one · 2012Article
- Design, synthesis, docking, and biological evaluation of novel diazide-containing isoxazole- and pyrazole-based histone deacetylase probes.Journal of medicinal chemistry · 2011Article
- Mammalian target of rapamycin: a central node of complex signaling cascades.International journal of clinical and experimental pathology · 2011Review
- Lipid raft-targeted Akt promotes axonal branching and growth cone expansion via mTOR and Rac1, respectively.Journal of neuroscience research · 2009Article
- Brought to life: targeted activation of enzyme function with small molecules.Journal of chemical biology · 2009Article
- Synergistic effect of ERK inhibition on tetrandrine-induced apoptosis in A549 human lung carcinoma cells.Journal of veterinary science · 2009Article
- Peptide-mediated activation of Akt and extracellular regulated kinase signaling prevents lymphocyte apoptosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2008Article
- An essential role for Akt1 in dendritic cell function and tumor immunotherapy.Nature biotechnology · 2006Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The anti-apoptotic Akt kinase is commonly activated by survival factors following plasma membrane relocalization attributable to the interaction of its pleckstrin homology (PH) domain with phosphatidylinositol 3-kinase (PI3K)-generated PI3,4-P(2) and PI3,4,5-P(3). Once activated, Akt can prevent or delay apoptosis by phosphorylation-dependent inhibition or activation of multiple signaling molecules involved in apoptosis, such as BAD, caspase-9, GSK3, and NF-kappaB and forkhead family transcription factors. Here, we describe and characterize a novel, conditional Akt controlled by chemically induced dimerization (CID). In this approach, the Akt PH domain has been replaced with the rapamycin (and FK506)-binding domain, FKBP12, to make F3-DeltaPH.Akt. To effect membrane recruitment, a myristoylated rapamycin-binding domain from FRAP/mTOR, called M-FRB, binds to lipid permeable rapamycin (and non-bioactive synthetic 'rapalogs'), leading to reversible heterodimerization of M-FRB with FKBP-DeltaPH.Akt. Like endogenous c-Akt, we show that the kinase activity of membrane-localized F3-DeltaPH.Akt correlates strongly with phosphorylation at T308 and S473; however, unlike c-Akt, phosphorylation and activation of inducible Akt (iAkt) is largely PI3K independent. CID-mediated activation of iAkt results in phosphorylation of GSK3, and contributes to NF-kappaB activation in vivo in a dose-sensitive manner. Finally, in Jurkat T cells stably expressing iAkt, CID-induced Akt activation rescued cells from apoptosis triggered by multiple apoptotic stimuli, including staurosporine, anti-Fas antibodies, PI3K inhibitors and the DNA damaging agent, etoposide. This novel inducible Akt should be useful for identifying new Akt substrates and for reversibly protecting tissue from apoptosis due to ischemic injury or immunological attack.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.